| 1. |
- Hill, Daniel, et al.
(författare)
-
Microfluidic and Transducer Technologies for Lab on a Chip Applications
- 2010
-
Ingår i: 2010 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC). - : IEEE conference proceedings. - 9781424441242 ; , s. 305-307
-
Konferensbidrag (refereegranskat)abstract
- Point-of-care diagnostic devices typically require six distinct qualities: they must deliver at least the same sensitivity and selectivity, and for a cost per assay no greater than that of today's central lab technologies, deliver results in a short period of time (<15 min at GP; <2h in hospital), be portable or at least small in scale, and require no or extremely little sample preparation. State-of-the-art devices deliver information of several markers in the same measurement.
|
|
| 2. |
- Volk, Anna-Luisa, et al.
(författare)
-
Bispecific Antibody Molecule Inhibits Tumor Cell Proliferation More Efficiently Than the Two-Molecule Combination
- 2021
-
Ingår i: Drugs in R&D. - : Adis. - 1174-5886 .- 1179-6901. ; 21:2, s. 157-168
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Monoclonal antibodies (mAbs) have proved to be a valuable tool for the treatment of different cancer types. However, clinical use of an increasing number of mAbs, have also highlighted limitations with monotherapy for cancers, in particular for such with more complex mechanisms, requiring action on additional molecules or pathways, or for cancers quickly acquiring resistance following monotherapy. An example for the latter is the mAb trastuzumab, FDA approved for treatment of metastatic gastric carcinoma. To circumvent this, researchers have reported synergistic, anti-proliferative effects by combination targeting of HER2 and EGFR by trastuzumab and the EGFR-targeting mAb Cetuximab overcoming trastuzumab resistance. Methods: Maintaining the proven functionality of trastuzumab, we have designed bi-specific antibody molecules, called AffiMabs, by fusing an EGFR-targeting Affibody molecule to trastuzumab’s heavy or light chains. Having confirmed binding to EGFR and Her2 and cytotoxicity of our AffiMabs, we analyzed apoptosis rate, receptor surface levels, phosphorylation levels of receptors and associated signaling pathways as well as differentially expressed genes on transcriptome level with the aim to elucidate the mode of action of our AffiMabs. Results: The AffiMabs are able to simultaneously bind HER2 and EGFR and show increased cytotoxic effect compared to the original trastuzumab therapeutic molecule and, more importantly, even to the combination of trastuzumab and EGFR-targeting Affibody molecule. Analyzing the mode of action, we could show that bi-specific AffiMabs lead to reduced surface receptor levels and a downregulation of cell cycle associated genes on transcriptome level. Conclusion: Our study shows that transcriptome analysis can be used to validate the choice of receptor targets and guide the design of novel multi-specific molecules. The inherent modularity of the AffiMab format renders it readily applicable to other receptor targets.
|
|
| 3. |
- Banerjee, Indradumna, 1986-, et al.
(författare)
-
LDH based neonatal diagnostics on a low-cost slipdisc based sample preparation platform.
- 2016
-
Konferensbidrag (refereegranskat)abstract
- INTRODUCTIONSlipdisc is developed as a sample preparation platform based on slipchip technology [1], using a handwinded clockwork mechanism allowing sample processing from one spot to another with defined precision without the need for sophisticated tools or alignment (Fig.1). An ordinary smartphone or camera can be used to image and analyse the results making it an ideal tool for resource limited settings. Here, we demonstrate a bioassay for detecting LDH (Fig.2), a crucial enzyme found in all living cells which leaks out when the cellular membrane is damaged. This makes LDH a biomarker for several medical conditions in newborns, such as Ozkiraz-13, necrotizing enterocolitis (NEC), and Asphyxia.EXPERIMENTALFor assembling the slipdisc optically transparent, robust and disposable CD like polycarbonate discs were used with superhydrophobic coating on all except the embedded microfluidic channels. For the LDH assay, heparinized plasma samples were spiked with 7 different concentrations of the LDH enzyme (Lee Biosolutions, USA). These concentrations ranged from clinically normal to abnormal concentrations and used to construct a standard curve for LDH enzyme.RESULTS AND DISCUSSIONThe ability of the SlipDisc to quantify LDH enzyme levels from plasma samples was evaluated (Fig.3). Using 7 different concentrations, a standard curve with clinically relevant LDH concentrations was obtained (Fig4). Image and data analyses, including linear regression and Pearson’s correlation, were completed using Image processing tool in Matlab.CONCLUSIONWe demonstrate a low-cost neonatal diagnostics platform for the detection of LDH from plasma using a novel SlipDisc platform. The SlipDisc can further be modified to separate plasma from whole blood samples in order to fully integrate the assay. Its simple operation and smartphone based detection capabilities make it an ideal device for point-of-care neonatal diagnostics.
|
|
| 4. |
- Hansson, Jonas, et al.
(författare)
-
Inertial microfluidics in parallel channels for high-throughput applications
- 2012
-
Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 12:22, s. 4644-4650
-
Tidskriftsartikel (refereegranskat)abstract
- Passive particle focusing based on inertial microfluidics was recently introduced as a high-throughput alternative to active focusing methods that require an external force-field to manipulate particles. In this study, we introduce inertial microfluidics in flows through straight, multiple parallel channels. The scalable, single inlet and two outlet, parallel channel system is enabled by a novel, high-density 3D PDMS microchannel manufacturing technology, mediated via a targeted inhibition of PDMS polymerization. Using single channels, we first demonstrate how randomly distributed particles can be focused into the centre position of the channel in flows through low aspect ratio channels and can be effectively fractionated. As a proof of principle, continuous focusing and filtration of 10 μm particles from a suspension mixture using 4- and 16-parallel-channel devices with a single inlet and two outlets are demonstrated. A filtration efficiency of 95-97% was achieved at throughputs several orders of magnitude higher than previously shown for flows through straight channels. The scalable and low-footprint focusing device requiring neither external force fields nor mechanical parts to operate is readily applicable for high-throughput focusing and filtration applications as a stand-alone device or integrated with lab-on-a-chip systems.
|
|
| 5. |
- Hansson, Jonas, et al.
(författare)
-
Inertial Particle Focusing In Parallel Microfluidic Channels For High-Throughput Filtration
- 2011
-
Ingår i: 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 2011. - : IEEE conference proceedings. - 9781457701573 ; , s. 1777-1780
-
Konferensbidrag (refereegranskat)abstract
- In this study, we introduce inertial microfluidics in straight, parallel channels for high-throughput particle filtration. We show that particles flowing through low aspect ratio rectangular microchannels can be focused into four particle streams, distributed at the centers of each wall face, or into two particle streams, at the centers of the longest channel walls, depending on the particles' size. For high-throughput filtration, we fabricated scalable, single inlet and two outlet, parallel channel microdevices, using a high-density 3D microfluidic PDMS channel manufacturing technology, in a design that allows for easy integration with other downstream on-chip functions we recently described. We demonstrate filtration of 24 μm particles from a suspension mixture in a microdevice with four parallel channels. The filtration efficiency at a non-optimized flow rate of 0.8 ml/min was 82%.
|
|
| 6. |
- Karlsson, J. Mikael, 1982-, et al.
(författare)
-
Fabrication and transfer of fragile 3D PDMS microstructures
- 2012
-
Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 22:8, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- We present a method for PDMS microfabrication of fragile membranes and 3D fluidic networks, using a surface modified water-dissolvable release material, poly(vinyl alcohol), as a tool for handling, transfer and release of fragile polymer microstructures. The method is well suited for the fabrication of complex multilayer microfluidic devices, here shown for a PDMS device with a thin gas permeable membrane and closely spaced holes for vertical interlayer connections fabricated in a single layer. To the authors knowledge, this constitutes the most advanced PDMS fabrication method for the combination of thin, fragile structures and 3D fluidics networks, and hence a considerable step in the direction of making PDMS fabrication of complex microfluidic devices a routine endeavour.
|
|
| 7. |
- Karlsson, J. Mikael, et al.
(författare)
-
On-Chip Liquid Degassing With Low Water Loss
- 2010
-
Ingår i: Proceedings Micro Total Analysis Systems (μTAS) 2010. - Groningen : CBMS. - 9780979806438 ; , s. 1790-1792
-
Konferensbidrag (refereegranskat)abstract
- We present a novel approach for actively degassing liquid and removing trapped air bubbles in microfluidic devices.In our approach, an integrated gas permeable membrane, consisting of a structurally supporting PDMS layer that is covered with a thin Teflon® AF 1600 film, separates the on-chip liquid from an on-chip low-vacuum chamber. Since the Teflon AF permeability is near zero for liquid water and low for vapour, air bubbles and dissolved air are removed through the membrane whilst the loss of water, ions and biomolecules in the system remains low. The system has been demonstrated at elevated temperatures and could be suitable for e.g. degassing during on-chip PCR.
|
|
| 8. |
- Lundgren, Stina, et al.
(författare)
-
Micro reactors for the optimisation of reaction conditions in asymmetric metal catalysis
- 2005
-
Ingår i: Micro Total Analysis Systems 2004. - 0854046437 ; , s. 445-447
-
Konferensbidrag (refereegranskat)abstract
- Two types of micro reactors were employed for enantioselective metal catalysed reactions. In the first type of reactor, an electroosmotic flow was used, whereas the second type of reactor used a pressure driven flow. The purpose of the study is to develop tools for rapid and efficient optimization of reactions, utilising minimum amounts of reagents.
|
|
| 9. |
- Pavankumar, A. R., et al.
(författare)
-
Bioanalytical advantages of a novel recombinant apyrase enzyme in ATP-based bioluminescence methods
- 2018
-
Ingår i: Analytica Chimica Acta. - : Elsevier. - 0003-2670 .- 1873-4324. ; 1025, s. 118-123
-
Tidskriftsartikel (refereegranskat)abstract
- Ultrasensitive measurements of intracellular ATP (intATP) based on the firefly luciferase reactions are frequently used to enumerate bacterial or mammalian cells. During clinical applications, extracellular ATP (extATP) should be depleted in biological samples since it interferes with intATP and affects the quantification of bacteria. The extATP can be eliminated by ATP-degrading enzymes but complete hydrolysis of extATP remains a challenge for today's commercial enzymes. The catalytic efficiency of ATP-degrading enzymes depends on enzyme characteristics, sample composition and the ability to deplete diphosphates, triphosphates and their complexes generated during the reaction. This phenomenon restricts the usage of bioluminescence-based ATP methods in clinical diagnostics. In light of this, we have developed a recombinant Shigella flexneri apyrase (RSFA) enzyme and analysed its ATP depletion potential with five commercial biochemical sources including potato apyrase, acid phosphatase, alkaline phosphatase, hexokinase and glycerol kinase. The RSFA revealed superior activity by completely eliminating the extracellular ATP and ATP-complexes, even in biological samples like urine and serum. Therefore, our results can potentially unwrap the chemical and bio-analytical applications of ATP-based bioluminescence tests to develop highly sensitive point-of-care diagnostics.
|
|
| 10. |
- Ramachandraiah, Harisha, et al.
(författare)
-
Centrifugal microfluidic system for rapid, low-cost HIV diagnosis : CD4+ T-cell counting using an integrated DVD platform
- 2012
-
Ingår i: Proceedings of the 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2012. - : Chemical and Biological Microsystems Society. - 9780979806452 ; , s. 1942-1944
-
Konferensbidrag (refereegranskat)abstract
- HIV is a pandemic that currently threatens over 33 million lives worldwide and HIV/AIDS remains one of the major causes of death globally. The continued monitoring of the CD4+ T-lymphocytes count in HIV patients is necessary for proper treatment, although this testing is too expensive and complex for limited resource settings. We report on a novel integrated centrifugal (CD) microfluidic system for rapid and low-cost HIV diagnosis through automated counting of CD4+ T-cells for point-of-care applications. We demonstrate the integrated T-cell immunocapture and detection mechanism using a novel system comprised of a modified commercial DVD drive and polymer disc.
|
|
